The hidden peril: Severe cutaneous reactions and their devastating outcomes in pediatric antiepileptic drug users

Objective This study aims to evaluate the risk, clinical outcomes, and age-specific characteristics of AED-associated SCARs in minors compared to adults using data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database. Methods A retrospective analysis was conducted using FAERS data from 2013 to Q3 2024. SCAR cases associated with AED use were identified and stratified by age groups (adults and minors) and further subdivided into pediatric age categories (0–2 years, 2–6 years, 6–12 years, and 12–18 years). Disproportionality analysis using reporting odds ratios (RORs) was performed to assess the risk of SCARs in minors compared to adults. Drug-specific and age-stratified analyses were conducted to elucidate patterns of SCAR occurrence and severity. Results Among 48,411 adverse drug reaction (ADR) cases in minors, 2472 (5.11%) were classified as SCARs. Minors exhibited significantly higher RORs for SCARs compared to adults, with the most pronounced risk signals observed for SJS-TEN overlap (ROR: 10.16, 95% CI: 7.27–14.21), SJS (ROR: 4.36, 95% CI: 4.03–4.73), and DRESS (ROR: 3.75, 95% CI: 3.53–3.98). SCARs in minors were associated with severe outcomes, including hospitalization (52.27%), life-threatening events (19.66%), and death (5.10%). Age-stratified analysis revealed distinct patterns of SCAR occurrence and severity across pediatric age groups. For example, infants (0–2 years) exhibited the highest ROR for DRESS (ROR: 83.01), while children aged 6–12 years showed the highest ROR for SJS-TEN overlap (ROR: 217.44). Lamotrigine (LTG), levetiracetam (LEV), and carbamazepine (CBZ) were the most frequently implicated AEDs, accounting for 33.37%, 21.44%, and 10.84% of pediatric SCAR cases, respectively. Notably, the median time to onset of SCARs was significantly shorter in minors (437 days) compared to adults (1497 days, P < 0.0001). Conclusions Minors face significantly higher AED-SCAR risk with earlier onset and greater severity, with marked heterogeneity across pediatric age groups. Lamotrigine showed the strongest association, but levetiracetam—often perceived as safer—ranked second in absolute SCAR reports, warranting a more cautious clinical approach. These findings underscore the need for age-specific monitoring and enhanced pharmacovigilance. Future research should prioritize prospective cohort studies, pharmacogenomics, and the development of databases that can track AED combination therapy risks in minors, a critical missing safety evidence gap.